contributed equally to this work. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: mitochondrial DNA (mtDNA); ribosomal RNA (rRNA); transfer RNA (tRNA); succinate dehydrogenase (SDH).

contributed equally to this work. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: mitochondrial DNA (mtDNA); ribosomal RNA (rRNA); transfer RNA (tRNA); succinate dehydrogenase (SDH).

Mitochondrial DNA (mtDNA) mutations accumulate in a number of ageing tissues and are proposed to play a role in the ageing process. We have previously shown that colonic crypt stem cells accumulate somatic mtDNA point mutations during ageing. These mtDNA mutations result in the loss of the activity of complex IV (cytochrome c oxidase (COX)) of the respiratory chain in the stem cells and their progeny, producing colonic crypts which are entirely COX deficient. However it is not known whether the other complexes of the respiratory chain are similarly affected during ageing. Here we have used antibodies to individual subunits of complexes I–IV to investigate their expression in the colonic epithelium from human subjects aged 18–84. We show that in ∼50% of crypts with any form of respiratory chain deficiency, decreased expression of subunits of multiple complexes is observed. Furthermore we have sequenced the entire mitochondrial genome of a number of cells with multiple complex defects and have found a wide variety of point mutations in these cells affecting a number of different protein encoding and RNA encoding genes. Finally we discuss the possible mechanisms by which multiple respiratory chain complex defects may occur in these cells.

Anal sphincter pressures, rectal compliance and sensation in 19 women of mean age 77 (range 57-94) years were studied before and after Delorme's procedure for full-thickness rectal prolapse. No patient had significant problems with defaecation after operation. There were no significant changes in anal sphincter pressures but the volume of first rectal sensation decreased from a median of 140 ml before surgery to 65 ml after the procedure (P = 0.01) and the maximum tolerated rectal volume declined from a median of 249 ml to 120 ml (P = 0.001). Rectal compliance was reduced from a median of 142.9 ml/kPa to 12.2 ml/kPa (P = 0.002). Improved rectal sensation and lowered compliance are associated with a reduced incidence of defaecatory problems after Delorme's procedure.

Studies of rectal sensory thresholds and compliance in patients with the irritable bowel syndrome have produced conflicting results though there is persistent evidence of rectal hypersensitivity particularly in those with diarrhoea-predominant symptoms. This study examined rectal sensation and compliance in 31 patients with constipation-predominant irritable bowel syndrome (mean age 41 years, 27 female) and 17 healthy volunteers (mean age 45 years, 17 female). A rectal balloon was inflated with fluid at a constant rate and the volume and intrarectal pressure at sensory threshold was recorded. The volumes at first (129 +/- 8 vs 229 +/- 24 ml, P < 0.001 Mann-Whitney-U test), constant (159 +/- 12 vs 286 +/- 21, P < 0.001) and maximum tolerated sensation (290 +/- 13 vs 509 +/- 19, P < 0.001) were all significantly less in the irritable bowel group. There was no significant difference in intrarectal pressures at any of these volumes (29.0 +/- 2.2 cmH2O vs 29.0 +/- 2.5, 35.0 +/- 2.5 vs 34.0 +/- 2.8, 71 +/- 2.5 vs 65.0 +/- 3.0 respectively). Rectal compliance was significantly less in the irritable bowel group (3.6 +/- 0.2 ml/cmH2O vs 8.7 +/- 0.4, P < 0.001). Twenty two patients complained of abdominal pain on balloon inflation, mimicking that experienced as part of their symptoms. Patients with constipation-predominant irritable bowel syndrome have rectal hypersensitivity and reduced compliance.

ObjectivesSacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering chronic constipation. Patients are currently selected for SNS using a 2week peripheral nerve evaluation (PNE) comprising stimulation via temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation. MethodsA randomised double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients demonstrating a reduction ≥ 0.5 in constipation symptom score (PAC-SYM) at 6 months. ResultsA total of 45 patients were randomised, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, 7 (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were non-responders. Six patients were withdrawn during the test phase due to infection or non-compliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60% vs 57%, p=0.76). The study was terminated prematurely due to a persistent infection rate of 10 (22%) during ePNE of which 9 (20%) were severe. ConclusionsePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6 week PNE poses a high risk of infection.

Background-Obstructive jaundice is associated with an increased incidence of infection and endotoxaemia, which may result from impaired host immunity. Neutrophil adhesion to vascular endothelium is a key part of the inflammatory response.Aims-To investigate neutrophil adhesion molecule expression and activation in obstructive jaundice. Patients-Nine adult patients with obstructive jaundice and 11 control subjects. Methods-The expression of the neutrophil adhesion receptors L-selectin, CD1 la, CD11b, CD1lc, and CD15 was determined using flow cytometry. CD1lb expression in response to stimulation with fMLP and endotoxin was measured. (Gut 1996; 38: 784-787)

These observations should prompt the careful assessment of cleaning techniques. The use of washing machines that do not recycle rinse water may avoid this complication.